Mobile Microfluidics

Abstract

Microfluidics platforms can program small amounts of fluids to execute a bio-protocol, and thus, can automate the work of a technician and also integrate a large part of laboratory equipment. Although most microfluidic systems have considerably reduced the size of a laboratory, they are still benchtop units, of a size comparable to a desktop computer. In this paper, we argue that achieving true mobility in microfluidics would revolutionize the domain by making laboratory services accessible during traveling or even in daily situations, such as sport and outdoor activities. We review the existing efforts to achieve mobility in microfluidics, and we discuss the conditions mobile biochips need to satisfy. In particular, we show how we adapted an existing biochip for mobile use, and we present the results when using it during a train ride. Based on these results and our systematic discussion, we identify the challenges that need to be overcome at technical, usability and social levels. In analogy to the history of computing, we make some predictions on the future of mobile biochips. In our vision, mobile biochips will disrupt how people interact with a wide range of healthcare processes, including medical testing and synthesis of on-demand medicine.

Keywords: healthcare; microfluidic biochips; mobility.

Figure 1

We depict schematically the bio-protocol called “Ovation Target Enrichment Technology for DNA”, developed by NuGEN Technology Inc. [1]. As illustrated, the duration of the bio-protocol is of 3.5 h, out of which 90 min of manual pipetting.

Figure 2

The automated setup for executing a bio-protocol on a digital microfluidic biochip: after the bio-protocol is designed, it is compiled automatically into an “electrode actuation sequence”, which controls the movement of droplets to run the bio-protocol. The droplet control instructions are stored on a microcontroller and triggered after the biochip has been loaded with the required fluids.

Figure 3

Transitioning towards mobile microfluidics implies that the instruments are operated from a battery (a), hand-held (c) and used in similar contexts as a smartphone (b,c).

Figure 4

A glucose meter is a commercial instrument that uses capillary microfluidics to measure glucose levels in blood droplets. It is operated from a battery and can be used in mobile scenarios.

Figure 5

Mixing in a flow channel microfluidic chip. (a) The lower valves are closed allowing the first fluid to fill the upper part of the mixer. Similarly, by closing the upper valves and opening the lower valves, the second fluid enters the chip. (b) The valves inside the rotary mixer are actuated one by one, thus generating a flow that mixes the fluids. (c) The mixed fluid exits the rotary mixer.

Figure 6

Publication count related to channel-based microfluidics. The count was retrieved from Google Scholar, by differential search between the topics “microfluidic” and “electrowetting microfluidics”. The values reported in this figure exclude patents and citations.

Figure 7

(a) Plugs (elongated droplets) are transported by the flow of the carrier oil that is continuously pumped through the micro-channels. (b) Plugs follow the direction of the oil flow along the channel, unless (c) there is a bifurcation that causes the plug to split.

Figure 8

(a) SAW biochips add interdigitated transducers orthogonal to the flow channels. When positioned at a bifurcation, the transducers can generate acoustic waves (similar to micro-earthquakes) that direct the plugs towards (b) the left channel or (c) the right channel.

Figure 9

An EWoD biochip transports droplets on an array of electrodes. (a) In the absence of voltage, the droplet does not wet the surface due to the hydrophobic layer that coats the electrode. (b) Electrical voltage unbalances the force equilibrium at the solid-liquid-vapor interface, causing the droplet to wet the surface. (c) Consequently, the droplet moves toward the charged electrode.

Figure 10

Illustration of the evolution of digital microfluidic biochips in the last years (from left to right): test microfluidic mixer developed by Duke University, a biochip for glucose assay, a device for parallel testing of 8 newborns for Pompe and Fabry diseases, DropBot—a generic do-it-yourself platform using chromium based electrodes, AM-EWOD biochip containing large array of electrodes (64 × 64) fabricated using thin-film transistor technology, biochips printed on paper using carbon nanotube ink, Neoprep—a benchtop device using digital microfluidics for sample preparation, OpenDrop—a cheap do-it-yourself biochip using printed circuit board technology.

Figure 11

Example in-vitro diagnosis bio-protocol modeled as a direct acyclic graph. In-vitro diagnosis is a template bio-protocol for identifying the microbes in the human samples using genetic testing. This bio-protocol performs a series of dilutions with specific reagents that trigger a colorimetric reaction. The microbial concentration is optically detected, by measuring the absorbance of the reaction product [103].

Figure 12

Each fluidic operation is modeled as a node with inputs and outputs. (a) A dispensing operation is a node with no predecessors, (b) a split operation divides one droplet into two equal daughter-droplets, (c) a merge operation combines together two droplets, (d) a mix operation transports a merged droplet over a specific route in order to achieve homogenous concentration, (e) a detection operation reads out a certain property of the droplet by means of an external sensor and (f) an incubation operation keeps the droplet at a constant temperature. For the detection and incubation, the biochip needs additional sensors and a temperature bar, respectively.

Figure 13

Example digital microfluidic platforms: (a) the three versions of OpenDrop [41] developed by Gaudilabs [105], (b) the latest version of DropBot [44] developed by Sci-Bots Inc. [106], and (c) the instrument developed by DigiBio B.V. [43]. The Dropbot photo is from R. Fobel and used with permission.

Figure 14

Direct comparison in size between (a) DropBot version 1 and OpenDrop version 1, and (b) OpenDrop version 3 and DigiBio instrument. The Dropbot photo is from R. Fobel and used with permission.

Figure 15

(a) Evaluating the robustness of OpenDrop under continuous shaking during a train trip. (b) Testing the water quality of a creek on a camping trip. We equipped OpenDrop with batteries, a cover to prevent damage to the electrodes and a cartridge with different reagents for basic health tests while on the go.

Figure 16

The experimental conditions (a–d) tilting the device in different orientations, at 45, 80, 90 and 180 degrees respectively.

Figure 17

Publication count related to digital microfluidics. The count was retrieved from Google Scholar, by searching for “electrowetting microfluidics”. The values reported in this figure exclude patents and citations.